US6262126B1 - Semi-fluorinated alkanes and their use - Google Patents
Semi-fluorinated alkanes and their use Download PDFInfo
- Publication number
- US6262126B1 US6262126B1 US09/043,489 US4348998A US6262126B1 US 6262126 B1 US6262126 B1 US 6262126B1 US 4348998 A US4348998 A US 4348998A US 6262126 B1 US6262126 B1 US 6262126B1
- Authority
- US
- United States
- Prior art keywords
- perfluoralkyl
- group
- branched
- linear
- alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0026—Blood substitute; Oxygen transporting formulations; Plasma extender
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/02—Halogenated hydrocarbons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/04—Artificial tears; Irrigation solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/23—Preparation of halogenated hydrocarbons by dehalogenation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
- C07C17/263—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions
- C07C17/269—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions of only halogenated hydrocarbons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
- C07C17/272—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by addition reactions
- C07C17/275—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by addition reactions of hydrocarbons and halogenated hydrocarbons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C19/00—Acyclic saturated compounds containing halogen atoms
- C07C19/08—Acyclic saturated compounds containing halogen atoms containing fluorine
-
- C—CHEMISTRY; METALLURGY
- C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
- C10L—FUELS NOT OTHERWISE PROVIDED FOR; NATURAL GAS; SYNTHETIC NATURAL GAS OBTAINED BY PROCESSES NOT COVERED BY SUBCLASSES C10G, C10K; LIQUEFIED PETROLEUM GAS; ADDING MATERIALS TO FUELS OR FIRES TO REDUCE SMOKE OR UNDESIRABLE DEPOSITS OR TO FACILITATE SOOT REMOVAL; FIRELIGHTERS
- C10L1/00—Liquid carbonaceous fuels
- C10L1/10—Liquid carbonaceous fuels containing additives
- C10L1/14—Organic compounds
- C10L1/20—Organic compounds containing halogen
- C10L1/201—Organic compounds containing halogen aliphatic bond
-
- C—CHEMISTRY; METALLURGY
- C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
- C10L—FUELS NOT OTHERWISE PROVIDED FOR; NATURAL GAS; SYNTHETIC NATURAL GAS OBTAINED BY PROCESSES NOT COVERED BY SUBCLASSES C10G, C10K; LIQUEFIED PETROLEUM GAS; ADDING MATERIALS TO FUELS OR FIRES TO REDUCE SMOKE OR UNDESIRABLE DEPOSITS OR TO FACILITATE SOOT REMOVAL; FIRELIGHTERS
- C10L1/00—Liquid carbonaceous fuels
- C10L1/10—Liquid carbonaceous fuels containing additives
- C10L1/14—Organic compounds
- C10L1/20—Organic compounds containing halogen
- C10L1/206—Organic compounds containing halogen macromolecular compounds
- C10L1/207—Organic compounds containing halogen macromolecular compounds containing halogen with or without hydrogen
-
- C—CHEMISTRY; METALLURGY
- C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
- C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
- C10M105/00—Lubricating compositions characterised by the base-material being a non-macromolecular organic compound
- C10M105/50—Lubricating compositions characterised by the base-material being a non-macromolecular organic compound containing halogen
- C10M105/52—Lubricating compositions characterised by the base-material being a non-macromolecular organic compound containing halogen containing carbon, hydrogen and halogen only
-
- C—CHEMISTRY; METALLURGY
- C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
- C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
- C10M107/00—Lubricating compositions characterised by the base-material being a macromolecular compound
- C10M107/38—Lubricating compositions characterised by the base-material being a macromolecular compound containing halogen
-
- C—CHEMISTRY; METALLURGY
- C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
- C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
- C10M131/00—Lubricating compositions characterised by the additive being an organic non-macromolecular compound containing halogen
- C10M131/02—Lubricating compositions characterised by the additive being an organic non-macromolecular compound containing halogen containing carbon, hydrogen and halogen only
- C10M131/04—Lubricating compositions characterised by the additive being an organic non-macromolecular compound containing halogen containing carbon, hydrogen and halogen only aliphatic
-
- C—CHEMISTRY; METALLURGY
- C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
- C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
- C10M147/00—Lubricating compositions characterised by the additive being a macromolecular compound containing halogen
- C10M147/02—Monomer containing carbon, hydrogen and halogen only
-
- C—CHEMISTRY; METALLURGY
- C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
- C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
- C10M2211/00—Organic non-macromolecular compounds containing halogen as ingredients in lubricant compositions
- C10M2211/02—Organic non-macromolecular compounds containing halogen as ingredients in lubricant compositions containing carbon, hydrogen and halogen only
- C10M2211/022—Organic non-macromolecular compounds containing halogen as ingredients in lubricant compositions containing carbon, hydrogen and halogen only aliphatic
-
- C—CHEMISTRY; METALLURGY
- C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
- C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
- C10M2211/00—Organic non-macromolecular compounds containing halogen as ingredients in lubricant compositions
- C10M2211/06—Perfluorinated compounds
-
- C—CHEMISTRY; METALLURGY
- C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
- C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
- C10M2213/00—Organic macromolecular compounds containing halogen as ingredients in lubricant compositions
- C10M2213/02—Organic macromolecular compounds containing halogen as ingredients in lubricant compositions obtained from monomers containing carbon, hydrogen and halogen only
-
- C—CHEMISTRY; METALLURGY
- C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
- C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
- C10M2213/00—Organic macromolecular compounds containing halogen as ingredients in lubricant compositions
- C10M2213/06—Perfluoro polymers
- C10M2213/062—Polytetrafluoroethylene [PTFE]
Definitions
- This invention relates to semifluorinated alkanes of the general formulas
- R F is a linear or branched perfluoralkyl group and R H is a linear or branched, saturated (hydrocarbon)-alkyl group.
- the unbranched semifluorinated alkanes have the formulas:
- the branched semifluorinated alkanes can also contain within the perfluoralkyl groups FCX units
- a —CX 2 — group can be contained within a perfluoralkyl chain, and a —CY 2 — group within an alkyl chain.
- the invention furthermore relates to the use of these semifluorinated alkanes in medicine, pharmacy, biology and technology.
- These semifluorinated alkanes can be used as medicinal adjuvants, drugs for ophthalmology, as a vitreous humor substitute, as a dermal treatment for supporting oxygen transport in the skin, for instillation and fluid artificial respiration in surgical interventions and in emergency medical treatment, to facilitate breathing in divers, and as friction-reducing additives in lubricants and waxes.
- the semifluorinated diblock or triblock alkanes are of an entirely different structure. They consist of closed hydrocarbon-alkane groups, —(CH 2 ) n — and —(CHR H ) n — and —(CH 2 ) n H, which are bound directly to perfluoralkyl groups, —(CF 2 ) m — and —(CFR F )— and —(CF 2 )F, respectively.
- the perfluoralkyl part can also begin with a (CR F R F F)— grouping and terminate in a (CR H R H H) grouping.
- an —R F CR F — group can be bound, and within an alkyl chain an —R H CR H — group can be bound.
- the semifluorinated diblock or triblock alkanes are colorless liquids or solids. They are not attacked by strong acids or lyes or oxidants or nucleophiles, much less liable to metabolic or catabolic attack.
- the semifluorinated alkanes behave like modified perfluorocarbons, and the boiling points and melting points increase with increasing molecular mass (see FIGS. 1 and 2 ).
- Semifluorinated alkanes like the pure perfluorocarbons, have a high solubility for gases, including O 2 and CO 2 (about 40-50 and 130-150 vol. %, respectively).
- the semifluorinated alkanes are scarcely or not at all soluble.
- the semifluorinated alkanes are soluble both in perfluorocarbons and derivatives of perfluorocarbons (perfluorinated ethers of higher molecular weight, Hostinert®, Fomblin®, etc.) [see H. Meinert, A. Knooff, Biomat. Art. Cells & Immob. Biotech., 21 (1993) 583; H. Meinert, Fluorine in Medicine in the 21 st Century, Manchester (1994), paper 23; R. J. Twieg et al., Macromolecules 18 (1985) 1361; and J. Höpken et al., Macromol. Chem.
- the formation of the gel is due to the fact that the solvent hydrocarbons are absorbed by the diblock double layers of the R F R H [R. J. Twieg et al., Macromolecules 18 (1985) 1361; J. Höpken et al., Macromol. Chem. 189 (1988) 911].
- the densities of the semifluorinated alkanes with densities between 1.1 and 1.7 g/cm 3 are substantially lower due to the fact that these molecules have a high content of hydrocarbon groupings.
- the proposed compounds have the preferred properties of the perfluorocarbons in regard to their boundary surface tension against water (R F R H 50-58 nN/m at 20° C.) and the extraordinarily low surface tension (R F R H 25-22 mN/m at 20° C., due to the fact that perfluoralkyl groups are bonded to the end of the molecule.
- the semifluorinated diblock or triblock alkanes are obtained by the reaction of perfluoralkyl iodides with alkenes or ⁇ , ⁇ — dienes, after HI elimination followed by hydrogenation by means of a platinum catalyst Organikum, autorenkollektiv, Dtsch. Verlag dermaschineen, Berlin (1977) 363 or by means of tributyltin hydride [J. Höpken et al., Macromol. Chem. 189 (1988) 911] (see the Examples of syntheses of semifluorinated diblock and triblock alkanes below).
- the products thereby obtained for the proposed fields of application can, in a preferred embodiment, also be highly purified.
- the semifluorinated alkanes are first treated with acid permanganate solution in a manner similar to DE 42 05 341 (WO 93/16974), then they are refluxed or autoclaved for about 72 hours at 150-180° C. with a mixture of strong aqueous caustic soda solution (4-8 n), CaO or BaO, and a nucleophilic agent (e.g., secondary amine).
- the reaction product is finally obtained by means of a separatory funnel from the aqueous alkaline phase, which in a given case still contains alcohol, and the amine phase is separated, treated repeatedly in succession with dilute mineral acid, NaHCO 3 solution, distilled water, anhydrous Na 2 SO 4 and anhydrous CaCl 2 and fractionally distilled through an efficient column.
- the semifluorinated alkanes thus treated are found by infrared, IH-NMR, 19 F-NMR, and GC- /MS spectroscopy to be free of groupings which might lead by intramolecular HF elimination to the formation of toxic olefinic byproducts.
- a suitable quantitative method for the determination of groupings that can lead to the intramolecular cleavage of HF or to the exchange of a fluorine atom bound to the carbon by means of a nucleophilic agent is, according to DE 42 05 341 (WO 93/16974), the determination of ionizable fluoride in the reaction of the sample material with hexamethylenediamine in nonane or decane by several hours of heating at 120-150° C., and detecting any freed fluoride by means of an ion-sensitive electrode. After the purification process, accordingly, no more fluoride ions were detectable (detection limit for the fluoride concentration ⁇ 10 ⁇ 5 mol/l ⁇ 1 ).
- the highly purified semifluorinated alkanes show no inhibition of proliferation in regard to DNA and protein synthesis on HeLa or Molt4 or HEP 2 cell cultures.
- the semifluorinated alkanes named in accord with the invention are directly usable for medical, pharmaceutical and biological purposes.
- the semifluorinated alkanes according to the invention can find many different uses, namely the use of linear or branched semifluorinated alkanes as medical adjuvants, as drugs for ophthalmology, as vitreous humor substituted, as a dermal treatment agent, for fluid artificial respiration by intubation, and as a friction-reducing additive for lubricant oils and waxes.
- the liquid representatives of the semifluorinated alkanes can be used on account of their outstanding physical properties directly for the unfolding of the retina; they are suitable as very stable colorless fluids for laser coagulation, because no degradation products are formed by the laser beam.
- the semifluorinated alkanes according to the invention are suitable for retinal reattachment, the same as the pure perfluorocarbons U.S. Pat. No. 4,490,351 (EP 0 112 658) U.S. Pat. No. 5,397,805 (EP 0 493 677, DE 41 00 059 and the modified perfluorocarbons claimed in DE 42 11 958 (EP 0 563 446).
- linear or branched semifluorinated alkanes are especially appropriate for ophthalmic treatment, especially when they have a relatively high alkyl content, —(CH 2 ) n , —(CH 2 ) n H and their R H -substituted isomers, due to their ability to dissolve medication as well as their ability to be dyed.
- the semifluorinated alkanes according to the invention especially the diblock compounds of the R F R H type with a high R H content are suitable as solvents for the medications to be used in ophthalmology.
- medicaments such as 5-fluoruracil, Retinol® or Daucomycin among others are moderately to easily soluble.
- the semifluorinated alkanes of the invention especially the linear representatives of the R F R H , have good solubility in silicone oils.
- the semifluorinated alkanes are more soluble in silicone oils the higher the R H content is.
- the fluid semifluorinated diblock compounds C 6 F 13 C 8 H 17 or C 4 F 9 C 5 H 11 or C 2 F 5 C 8 H 17 are uniformly soluble.
- these R F R H 's dissolve in silicone oil of 1000 mPa/s in ratios of 2:1 to 1:2. The solubilities decrease as the viscosity of the silicone oil increases.
- the semifluorinated alkanes are solvents for perfluorocarbons it is also possible to transform solutions of perfluorocarbons to semifluorinated alkanes, especially of the R F R H type, with the corresponding silicone oils, to homogeneous, optically clear systems and then use them for the tamponade.
- EP 29 66 61 a single-phase system containing perfluorocarbon is described, which can act in the cosmetic field and as a lotion to promote oxygen transportation.
- Perfluorocarbons with a maximum concentration of 50% are emulsified in water with perfluorinated emulsifiers of the alkanesulfonic acid amide type in the presence of an aliphatic alcohol as an emulsifying aid.
- a skin remedy which, for the purpose of enhancing oxygen transport in the skin, consists of asymmetrical lamellar aggregates built up from phospholipids with a content of phosphatidyl choline ranging from 30 to 99 wt.-% which, unlike the well-known aqueous liposomes, contain perfluorocarbons or mixtures ranging from 1 to 100% w/v in a vehicle suitable for dermatological application.
- perfluoralkanes mono-or bicyclic, fluoralkyl-substituted perfluorocyclo alkanes, perfluorinated aliphatic or bicyclic amines, bis-(perfluoralkyl)-ethenes or mixtures thereof are described as perfluorocarbons, and of this group perfluorodecalin, perfluoroobutyltetrahydrofuran, perfluorotributylamine, perfluoroctyl bromide, bis-fluoro(butyl)-ethene or C 6 -C 9 perfluoralkanes are preferred.
- CST temperature the critical temperature of solubility in n-hexane
- the semifluorinated alkanes according to the invention are easily to moderately soluble in hydrocarbons and derivatives thereof, the solubility increasing as the R H content increases and the R F content decreasing in the semifluorinated alkane.
- the compounds C 2 F 5 -C 8 H 17 and C 4 F 9 -C 10 H 21 dissolve in thin to thick liquid paraffins which find use as pharmaceutical oils and adjuvants (60-230 mPa/s), pump oils or motor oils.
- R F R H 's are also soluble in silicone oils, as already explained.
- the transition temperatures of homogeneous, fluid solution and viscous gel are given for these systems in FIG. 3; for the claimed application purpose they are within an optimum range of skin and room temperature.
- the tissue penetration is due to the lipophilia of the oxygen carrier.
- Perfluorocarbons are far less lipophilic than the semifluorinated alkanes according to the invention, and their lipophilia is based on the R H part of the molecule.
- the CST temperature in the semifluorinated alkanes of the R F R H type is, entirely below ⁇ 22° C., while for most perfluorocarbons it is above +20° C.
- the use of the R F R H 's claimed according to the invention offers a significant advantage over all of the perfluorocarbon compounds described in U.S. Pat No. 4,366,169, GB 2087882, EP 29 66 61, DE 41 27 442, and DE 42 21 255.
- the semifluorinated alkanes according to the invention can be made very easily into stable, aqueous emulsions of the o/w and w/o types with asymmetrical lamellar aggregates, by means of biocompatible emulsifiers (natural phospholipids, such as soya or egg lecithin or synthetically prepared lecithins, or phospholipid mixtures with a content of 60-98% of phosphatidylcholine or ethylene oxide-propylene oxide block polymers, Pluronic®, etc.) with the aid of physical emulsification methods (ultrasound or Gaulin homogenizer, Ultraturrax dispersion machine).
- biocompatible emulsifiers natural phospholipids, such as soya or egg lecithin or synthetically prepared lecithins, or phospholipid mixtures with a content of 60-98% of phosphatidylcholine or ethylene oxide-propylene oxide block polymers, Pluronic®, etc.
- the systems thus prepared constitute the effective, gas-transporting substance in salves, cremes, pastes, lotions and other aqueous or alcoholic dermatological formulations as well as in powders.
- the skin remedy according to the invention can be applied to bandages, plasters, wound coverings and other means coming in contact with the skin.
- the salve bases according to the invention furthermore serve for protection against contact dermatitis.
- oxygen-saturated liquid perfluorocarbons such as perfluordecalin
- perfluordecalin oxygen-saturated liquid perfluorocarbons
- the medium carrying O 1 or CO 2 put into the lungs through the tube can be constantly enriched with O 2 by means of an oxygenator through a circulatory system and freed of CO 2 by means of a corresponding CO 2 trapping system.
- a diver thus supplied no longer needs to breathe air or oxygen from compressed-air bottles and exhale through a system of valves.
- the valve noises and the issuing gas and air bubbles enable the diver to be found by means of sensitive sonar systems.
- the advantage of the invention consists in the use of the fluid, liquid semifluorinated alkanes, especially C 6 F 13 C 8 H 17 (b.p. 220° C.), C 4 F 9 C 5 H 11 (b.p. 131° C.), C 2 F 5 C 8 H 17 (b.p. 159° C.), C 2 F 5 C 4 H 8 C 2 F 5 (b.p. 138° C.), C 2 F 5 C 6 H 12 C 2 F 5 (b.p. 200° C.), C 3 F 7 C 2 H 4 C 3 F 7 (b.p. 115° C.), C 3 F 7 C 4 H 8 C 3 F 7 (b.p. 180° C.).
- lubricant additives on the basis of monofluorinated or oligomeric fluorinated hydrocarbons are described, which contain in addition to CF bonds, bonds with weakly bonded moieties such as Cl, OH, OR, SH and SR, SR, R representing an amine and/or NH 4 +—, Ba 2 +—, or Zn 2 +— salt of monofluorophosphates or fluorophosphonates.
- the additives are described as usable for metal-to-metal surfaces in machines.
- perfluoralkyl ethers of low molecular weight are described as lubricants for extremely low temperatures, in outer space, for example.
- the semifluorinated alkanes according to the invention have outstanding properties as friction-reducing additives for highly stressed lubricant oils, waxes, hydraulic fluids and compressor fluids.
- semifluorinated alkanes are physically, chemically and physiologically inert. Due to the closed hydrocarbon-alkane groups, —(CH 2 ) m —, —(CHR H ) M —, —(R H CR H )—, —(CH 2 ) m H, —(CHR H ) m H, —(—(R H CR H )H), the CF bonds in the perfluoralkyl groups directly bonded thereto, —(CF 2 ) n —, —(CFR F )—, —(R F CR F )—, —(CF 2 )F, —(CFR F )F, and —(R F CR F )F, (in comparison with the CF bonds in the pure perfluorocarbons) are further strengthened. Intramolecular HF cleavage with the formation of fluorolefinic double bonds does not occur. Thus, for the application according to the invention as friction-
- the semifluorinated alkanes according to the invention are of an amphiphilic character.
- Especially compounds of the F(CF 2 ) n (CH 2 ) m H type are characterized by low boundary surface tensions (50-58 mN/m at 20° C.), and extraordinarily low surface tensions (15-22 mN/m at 20° C.), due to the fact that the oleophobic and lipophobic R F groups are bound to the one end of the molecule and the oleophilic and lipophilic R H groups are bound to the other end.
- the R F R H 's at the boundary surfaces of these systems arrange themselves such that their R H part reaches into the solvent containing hydrocarbons, while the oleophobic R F part reaches outward.
- the diblock compounds F(CF 2 ) n (CH 2 ) m (CF 2 ) n F since in the longer-chain molecules, due to the steric arrangement of the molecule, the R F groups of both ends arrange themselves unilaterally against the long-chain alkane bonding link. The result is the reduction of friction on metal surfaces or ceramic surfaces or polymeric carbon fibers or structures, etc. Furthermore, the result is also a barrier effect against the escape of volatile solvent molecules through these boundary layers.
- solubility in hydrocarbons and their derivatives increases with a high percentage of alkyl groups, and therefore also in silicone oils, in the case of the R F R H with increasing R H content and decreasing R F content.
- the compounds C 2 F 5 C 8 H 17 (b.p. 160° C.), C 4 F 9 C 5 H 11 (b.p. 131° C.), C 6 F 13 C 8 H 17 (b.p. 20 104° C.), C 10 F 21 C 12 H 25 (b.p. 64° C.) and C 12 F 25 C 20 H 41 (b.p. 98° C.) are easily soluble for the stated use and at the given concentrations (0.1-10 wt.-%).
- the barrier effect described above which is due to the orientation of the semifluorinated alkanes in the boundary surface, also reduces the flammability of lubricants and fuels.
- the additives according to the invention find use primarily in lubricating oils and waxes for closed systems.
- FIG. 3 is phase diagrams of C 10 F 21 C 12 H 25 (abbreviated: F 10 H 12 ) in octane, decane, hexadecane and cyclodecane according to R. J. Twieg et al., Macromolecules 18 (1985) 1361.
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Ophthalmology & Optometry (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Hematology (AREA)
- Pulmonology (AREA)
- Surgery (AREA)
- Toxicology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Materials For Medical Uses (AREA)
- External Artificial Organs (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/854,634 US6486212B2 (en) | 1995-09-29 | 2001-05-15 | Semifluorinated alkanes and the use thereof |
US09/854,594 US6489367B1 (en) | 1995-09-29 | 2001-05-15 | Semifluorinated alkanes and the use thereof |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19536504A DE19536504C2 (de) | 1995-09-29 | 1995-09-29 | Verwendung fluorierter Alkane |
DE19536504 | 1995-09-29 | ||
PCT/EP1996/003542 WO1997012852A1 (de) | 1995-09-29 | 1996-08-09 | Semifluorierte alkane und ihre verwendung |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1996/003542 A-371-Of-International WO1997012852A1 (de) | 1995-09-29 | 1996-08-09 | Semifluorierte alkane und ihre verwendung |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/854,594 Division US6489367B1 (en) | 1995-09-29 | 2001-05-15 | Semifluorinated alkanes and the use thereof |
US09/854,634 Division US6486212B2 (en) | 1995-09-29 | 2001-05-15 | Semifluorinated alkanes and the use thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
US6262126B1 true US6262126B1 (en) | 2001-07-17 |
Family
ID=7773697
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/043,489 Expired - Lifetime US6262126B1 (en) | 1995-09-29 | 1996-08-09 | Semi-fluorinated alkanes and their use |
US09/854,594 Expired - Lifetime US6489367B1 (en) | 1995-09-29 | 2001-05-15 | Semifluorinated alkanes and the use thereof |
US09/854,634 Expired - Lifetime US6486212B2 (en) | 1995-09-29 | 2001-05-15 | Semifluorinated alkanes and the use thereof |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/854,594 Expired - Lifetime US6489367B1 (en) | 1995-09-29 | 2001-05-15 | Semifluorinated alkanes and the use thereof |
US09/854,634 Expired - Lifetime US6486212B2 (en) | 1995-09-29 | 2001-05-15 | Semifluorinated alkanes and the use thereof |
Country Status (9)
Country | Link |
---|---|
US (3) | US6262126B1 (es) |
EP (3) | EP0859751B2 (es) |
JP (3) | JP2000511157A (es) |
KR (3) | KR100457157B1 (es) |
AT (3) | ATE214270T1 (es) |
CA (3) | CA2473393C (es) |
DE (4) | DE19536504C2 (es) |
ES (3) | ES2144259T5 (es) |
WO (1) | WO1997012852A1 (es) |
Cited By (45)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040197376A1 (en) * | 1999-06-12 | 2004-10-07 | Dirk-Henning Menz | Plastically deformable implant |
US20050095245A1 (en) * | 2003-09-19 | 2005-05-05 | Riley Thomas C. | Pharmaceutical delivery system |
WO2005117850A1 (en) * | 2004-06-01 | 2005-12-15 | The Trustees Of Columbia University In The City Ofnew York | Partially-fluorinated ethers, compositions and uses thereof, for long-term tamponade in the eye |
US7026359B1 (en) | 1999-06-12 | 2006-04-11 | Bausch & Lomb Incorporated | Utilization of a highly fluorinated oligomeric alkane in ophthalmology |
US20060193799A1 (en) * | 2002-09-24 | 2006-08-31 | Therox, Inc. | Method of Making Perfluorocarbon Emulsions With Non-Fluorinated Surfactants |
US20070224226A1 (en) * | 2006-01-05 | 2007-09-27 | Drugtech Corporation | Composition and method of use thereof |
US20100008996A1 (en) * | 2008-04-18 | 2010-01-14 | Novaliq Gmbh | Inhalative and instillative use of semifluorinated alkanes as an active substance carrier in the intrapulmonary area |
US20100274215A1 (en) * | 2007-11-19 | 2010-10-28 | Fluoron Gmbh | Flushing solution |
US20110034414A1 (en) * | 2008-04-28 | 2011-02-10 | Al.Chi.Mi.A. S.R.L. | Fluoroalkyloxy alkanes, process for production and uses thereof |
WO2011061332A1 (en) | 2009-11-23 | 2011-05-26 | Novaliq Gmbh | Pharmaceutical composition comprising propofol |
US20110137285A1 (en) * | 2009-12-04 | 2011-06-09 | Al.Chi.Mi.A. S.R.L. | Kit of tamponing liquids and a method for the treatment of tears and/or detachments of the retina using such liquids |
EP2335735A1 (en) * | 2009-12-14 | 2011-06-22 | Novaliq GmbH | Pharmaceutical composition for treatment of dry eye syndrome |
WO2011151079A3 (de) * | 2010-06-02 | 2012-05-03 | Fluoron Gmbh | Zubereitung zur verwendung in der augenheilkunde und netzhautchirurgie |
WO2012062834A1 (en) * | 2010-11-11 | 2012-05-18 | Novaliq Gmbh | Liquid pharmaceutical composition for the treatment of a posterior eye disease |
EP2708228A1 (en) | 2012-09-12 | 2014-03-19 | Novaliq GmbH | Eye wash compositions |
WO2014041071A1 (en) | 2012-09-12 | 2014-03-20 | Novaliq Gmbh | Semifluorinated alkane compositions |
US20140315767A1 (en) * | 2013-04-22 | 2014-10-23 | Basf Se | Seal Compatibility Additive To Improve Fluoropolymer Seal Compatibility of Lubricant Compositions |
US20150191673A1 (en) * | 2013-04-22 | 2015-07-09 | Basf Se | Lubricating Oil Compositions Containing A Halide Seal Compatibility Additive And A Second Seal Compatibility Additive |
EP2944324A1 (de) * | 2014-05-13 | 2015-11-18 | LTS LOHMANN Therapie-Systeme AG | Verwendung von semifluorierten Alkanen in transdermalen therapeutischen Systemen |
US20160022648A1 (en) * | 2013-03-13 | 2016-01-28 | Santen Pharmaceutical Co., Ltd. | Therapeutic agent for meibomian gland dysfunction |
US9308262B2 (en) | 2011-05-25 | 2016-04-12 | Novaliq Gmbh | Pharmaceutical composition for administration to nails |
WO2016082644A1 (en) * | 2014-11-26 | 2016-06-02 | The University Of Hong Kong | A semifluorinated alkane based cleaner for removing emulsified droplets in the eye to reduce the complications associated with the emulsification of silicone oil |
US20160264900A1 (en) * | 2013-11-05 | 2016-09-15 | Solvay Specialty Polymers Italy S.P.A. | Modified hydrocarbons |
CN106631681A (zh) * | 2016-11-29 | 2017-05-10 | 上海杰视医疗科技有限公司 | 含氟烷烃的纯化方法 |
US9757459B2 (en) | 2010-10-20 | 2017-09-12 | Novaliq Gmbh | Liquid pharmaceutical composition for the delivery of active ingredients |
US9757460B2 (en) | 2012-01-23 | 2017-09-12 | Novaliq Gmbh | Stabilised protein compositions based on semifluorinated alkanes |
CN107397718A (zh) * | 2011-05-25 | 2017-11-28 | 诺瓦利克有限责任公司 | 基于半氟化烷烃类的外用药物组合物 |
US10045996B2 (en) | 2010-03-17 | 2018-08-14 | Novaliq Gmbh | Pharmaceutical composition for treatment of increased intraocular pressure |
US10273298B2 (en) | 2013-07-23 | 2019-04-30 | Novaliq Gmbh | Stabilized antibody compositions |
US10369117B2 (en) | 2012-09-12 | 2019-08-06 | Novaliq Gmbh | Compositions comprising mixtures of semifluorinated alkanes |
WO2019185543A1 (en) * | 2018-03-28 | 2019-10-03 | Novaliq Gmbh | Pharmaceutical composition comprising timolol |
US10507132B2 (en) | 2016-06-23 | 2019-12-17 | Novaliq Gmbh | Topical administration method |
US10682315B2 (en) | 2015-09-30 | 2020-06-16 | Novaliq Gmbh | Semifluorinated compounds and their compositions |
US10717691B2 (en) | 2017-05-05 | 2020-07-21 | Novaliq Gmbh | Process for the production of semifluorinated alkanes |
US10813976B2 (en) | 2016-09-23 | 2020-10-27 | Novaliq Gmbh | Ophthalmic compositions comprising ciclosporin |
US11154513B2 (en) | 2015-09-30 | 2021-10-26 | Novaliq Gmbh | Semifluorinated compounds |
JP2022501343A (ja) * | 2018-09-27 | 2022-01-06 | ノバリック ゲーエムベーハー | 局所日焼け止め製剤 |
US11273174B2 (en) | 2017-04-21 | 2022-03-15 | Novaliq Gmbh | Iodine compositions |
US11278503B2 (en) | 2017-05-12 | 2022-03-22 | Novaliq Gmbh | Pharmaceutical compositions comprising semifluorinated alkanes for the treatment of contact lense-related conditions |
US11413323B2 (en) | 2018-10-12 | 2022-08-16 | Novaliq Gmbh | Ophthalmic composition for treatment of dry eye disease |
US11576893B2 (en) | 2018-03-02 | 2023-02-14 | Novaliq Gmbh | Pharmaceutical compositions comprising nebivolol |
US11684589B2 (en) | 2016-09-22 | 2023-06-27 | Novaliq Gmbh | Pharmaceutical compositions for use in the therapy of blepharitis |
US11723861B2 (en) | 2017-09-27 | 2023-08-15 | Novaliq Gmbh | Ophthalmic compositions comprising latanoprost for use in the treatment of ocular diseases |
US11896559B2 (en) | 2017-10-04 | 2024-02-13 | Novaliq Gmbh | Opthalmic compositions comprising F6H8 |
US12029757B2 (en) | 2018-09-27 | 2024-07-09 | Dermaliq Therapeutics, Inc. | Lipid barrier repair |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE19719280C1 (de) * | 1997-05-07 | 1998-09-24 | Pharm Pur Gmbh | Fluorierte Alkane und ihre Verwendungen |
DE19811683C2 (de) * | 1998-03-18 | 2000-03-23 | Pharm Pur Gmbh | Behandlungsmittel für die Ophthalmologie |
DE19861012A1 (de) | 1998-03-18 | 1999-09-30 | Pharm Pur Gmbh | Behandlungsmittel für die Ophthalmologie |
DE10336841A1 (de) * | 2003-08-11 | 2005-03-17 | Rovi Gmbh & Co. Kosmetische Rohstoffe Kg | Kosmetische Zusammensetzung zur Unterstützung des Sauerstofftransports in die Haut |
DE10358306B8 (de) | 2003-12-08 | 2005-03-03 | Coty B.V. | Kosmetisches und dermatologisches Sauerstoff-Trägersystem, Verfahren zu dessen Herstellung sowie seine Verwendung |
DE102005055811A1 (de) * | 2005-11-23 | 2007-05-31 | Novaliq Gmbh | Verwendung einer Zusammensetzung zur Konservierung von Organen und Gliedmaßen |
EP2274348B1 (en) * | 2008-03-04 | 2013-06-12 | Cornell University | Triblock polymers and polymer coatings |
DE202010009243U1 (de) | 2010-06-02 | 2011-09-19 | Fluoron Gmbh | Zubereitung |
CN102041142B (zh) * | 2010-12-25 | 2013-11-20 | 锦州惠发天合化学有限公司 | 一种含氟润滑油 |
CN102070493B (zh) * | 2011-01-04 | 2013-07-31 | 锦州惠发天合化学有限公司 | 一种含氟润滑油添加剂的制备方法 |
DK2661280T3 (en) * | 2011-01-04 | 2019-03-04 | Novaliq Gmbh | O / V EMULSIONS INCLUDING SEMIFLUORINATED ALKANES |
DE202013011832U1 (de) | 2012-04-11 | 2014-07-25 | Fluoron Gmbh | Färbemittel |
DE102012103097A1 (de) | 2012-04-11 | 2013-10-17 | Fluoron Gmbh | Färbemittel zum Einfärben einer ophthalmischen Membran |
EP2783703A1 (en) * | 2013-03-25 | 2014-10-01 | B. Braun Melsungen AG | Semifluorocarbon compound containing contrast agent |
DE202015101488U1 (de) | 2015-03-24 | 2016-06-28 | Fluoron Gmbh | Waschlösung |
GB2542406B (en) | 2015-09-18 | 2018-04-11 | Schlumberger Holdings | Determining properties of porous material by NMR |
BR112019006194A2 (pt) * | 2016-09-28 | 2019-06-18 | Novaliq Gmbh | composições que compreendem um ligante de ligação ao receptor de canabinóides |
US20200339492A1 (en) | 2017-06-12 | 2020-10-29 | Novaliq Gmbh | Process for the preparation of semifluorinated alkanes using grignard reagents |
KR20230142548A (ko) | 2021-02-03 | 2023-10-11 | 에이디에스 테라퓨틱스 엘엘씨 | 국소 안과용 조성물 |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2997505A (en) | 1954-07-12 | 1961-08-22 | Research Corp | Fluoro-nitro olefins |
GB1364495A (en) * | 1970-12-05 | 1974-08-21 | Hoechst Ag | Process for preparing fluorinated hydrocarbons |
US3979469A (en) * | 1972-12-21 | 1976-09-07 | Ciba-Geigy Corporation | Polyfluoroalkyl iodides, process for their manufacture, and their use |
DE3925525A1 (de) | 1989-08-02 | 1991-02-07 | Hoechst Ag | Verfahren zur herstellung von (alpha),omega-bisperfluoralkylalkanen |
EP0444752A1 (en) | 1990-03-02 | 1991-09-04 | ENICHEM SYNTHESIS S.p.A. | Agents affording sliding characteristics |
WO1993001798A1 (en) * | 1991-07-17 | 1993-02-04 | S.A. A.T.T.A. Applications Et Transferts De Technologies Avancees | Preparations comprising a fluorocarbon and a lipophilic/fluorophilic organic compound, and their uses |
EP0563446A1 (de) | 1992-04-01 | 1993-10-06 | PHARMPUR GmbH | Behandlungsmittel für die Augenheilkunde und seine Verwendung |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4173654A (en) * | 1977-01-03 | 1979-11-06 | California Institute Of Technology | Novel fluorohydrocarbons |
JPS63281218A (ja) * | 1987-05-13 | 1988-11-17 | Hitachi Ltd | 磁気記録媒体 |
-
1995
- 1995-09-29 DE DE19536504A patent/DE19536504C2/de not_active Revoked
-
1996
- 1996-08-09 ES ES96927711T patent/ES2144259T5/es not_active Expired - Lifetime
- 1996-08-09 DE DE59604257T patent/DE59604257D1/de not_active Expired - Lifetime
- 1996-08-09 WO PCT/EP1996/003542 patent/WO1997012852A1/de active IP Right Grant
- 1996-08-09 CA CA002473393A patent/CA2473393C/en not_active Expired - Fee Related
- 1996-08-09 AT AT99111588T patent/ATE214270T1/de not_active IP Right Cessation
- 1996-08-09 CA CA002232880A patent/CA2232880C/en not_active Expired - Lifetime
- 1996-08-09 EP EP96927711A patent/EP0859751B2/de not_active Expired - Lifetime
- 1996-08-09 JP JP09513914A patent/JP2000511157A/ja active Pending
- 1996-08-09 DE DE59608937T patent/DE59608937D1/de not_active Expired - Lifetime
- 1996-08-09 EP EP99111588A patent/EP0965334B1/de not_active Expired - Lifetime
- 1996-08-09 US US09/043,489 patent/US6262126B1/en not_active Expired - Lifetime
- 1996-08-09 ES ES99111588T patent/ES2174554T3/es not_active Expired - Lifetime
- 1996-08-09 AT AT96927711T patent/ATE188958T1/de active
- 1996-08-09 CA CA2473394A patent/CA2473394C/en not_active Expired - Fee Related
- 1996-08-09 KR KR10-1998-0702315A patent/KR100457157B1/ko not_active IP Right Cessation
- 1996-08-09 AT AT99105854T patent/ATE214589T1/de not_active IP Right Cessation
- 1996-08-09 ES ES99105854T patent/ES2174551T3/es not_active Expired - Lifetime
- 1996-08-09 KR KR10-2004-7007418A patent/KR100478789B1/ko not_active IP Right Cessation
- 1996-08-09 DE DE59608891T patent/DE59608891D1/de not_active Expired - Lifetime
- 1996-08-09 EP EP99105854A patent/EP0965329B1/de not_active Expired - Lifetime
- 1996-08-09 KR KR10-2004-7007419A patent/KR100497874B1/ko not_active IP Right Cessation
-
2001
- 2001-05-15 US US09/854,594 patent/US6489367B1/en not_active Expired - Lifetime
- 2001-05-15 US US09/854,634 patent/US6486212B2/en not_active Expired - Lifetime
-
2003
- 2003-10-02 JP JP2003344962A patent/JP4731801B2/ja not_active Expired - Fee Related
- 2003-10-02 JP JP2003344963A patent/JP2004083593A/ja active Pending
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2997505A (en) | 1954-07-12 | 1961-08-22 | Research Corp | Fluoro-nitro olefins |
GB1364495A (en) * | 1970-12-05 | 1974-08-21 | Hoechst Ag | Process for preparing fluorinated hydrocarbons |
US3979469A (en) * | 1972-12-21 | 1976-09-07 | Ciba-Geigy Corporation | Polyfluoroalkyl iodides, process for their manufacture, and their use |
DE3925525A1 (de) | 1989-08-02 | 1991-02-07 | Hoechst Ag | Verfahren zur herstellung von (alpha),omega-bisperfluoralkylalkanen |
EP0444752A1 (en) | 1990-03-02 | 1991-09-04 | ENICHEM SYNTHESIS S.p.A. | Agents affording sliding characteristics |
US5202041A (en) * | 1990-03-02 | 1993-04-13 | Enichem Synthesis S.P.A. | Ski lubricant comprising paraffinic wax and a hydrocarbon compound containing a perfluoro segment |
US5423994A (en) * | 1990-03-02 | 1995-06-13 | Enichem Synthesis S.P.A. | Ski lubricant comprising a hydrocarbon compound containing a perfluoro segment |
WO1993001798A1 (en) * | 1991-07-17 | 1993-02-04 | S.A. A.T.T.A. Applications Et Transferts De Technologies Avancees | Preparations comprising a fluorocarbon and a lipophilic/fluorophilic organic compound, and their uses |
EP0563446A1 (de) | 1992-04-01 | 1993-10-06 | PHARMPUR GmbH | Behandlungsmittel für die Augenheilkunde und seine Verwendung |
US5441733A (en) * | 1992-04-01 | 1995-08-15 | Pharmpur Gmbh | Treatment agent for ophthalmology and use thereof |
Non-Patent Citations (1)
Title |
---|
Twieg et al., "Synthesis and characterization of perfluoroalkylalkanes (PFAA) as models for semiflexible polymers," Chemical Abstracts, vol. 101, No. 2, Jul. 9, 1984. |
Cited By (112)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7026359B1 (en) | 1999-06-12 | 2006-04-11 | Bausch & Lomb Incorporated | Utilization of a highly fluorinated oligomeric alkane in ophthalmology |
US20040197376A1 (en) * | 1999-06-12 | 2004-10-07 | Dirk-Henning Menz | Plastically deformable implant |
US7101564B1 (en) | 1999-06-12 | 2006-09-05 | Pharm Pur Gmbh | Plastically deformable implant |
US6984394B2 (en) | 1999-06-12 | 2006-01-10 | Bausch & Lomb Incorporated | Plastically deformable implant |
US20060193878A1 (en) * | 2002-09-24 | 2006-08-31 | Therox, Inc. | Method of Preparing Gas Delivering Perfluorocarbon Emulsions With Non-Fluorinated Surfactants |
US20060193799A1 (en) * | 2002-09-24 | 2006-08-31 | Therox, Inc. | Method of Making Perfluorocarbon Emulsions With Non-Fluorinated Surfactants |
US7357937B2 (en) | 2002-09-24 | 2008-04-15 | Therox, Inc. | Perfluorocarbon emulsions with non-fluorinated surfactants |
US7468191B2 (en) | 2002-09-24 | 2008-12-23 | Therox, Inc. | Method of preparing gas delivering perfluorocarbon emulsions with non-fluorinated surfactants |
US9789057B2 (en) | 2003-09-19 | 2017-10-17 | Perrigo Pharma International Designated Activity Company | Pharmaceutical delivery system |
US20050095245A1 (en) * | 2003-09-19 | 2005-05-05 | Riley Thomas C. | Pharmaceutical delivery system |
WO2005117850A1 (en) * | 2004-06-01 | 2005-12-15 | The Trustees Of Columbia University In The City Ofnew York | Partially-fluorinated ethers, compositions and uses thereof, for long-term tamponade in the eye |
US20070219162A1 (en) * | 2004-06-01 | 2007-09-20 | The Trustees Of Columbia University In The City Of New York | Partially-fluorinated ethers, compositions and uses thereof, for long-term tamponade in the eye |
US20070224226A1 (en) * | 2006-01-05 | 2007-09-27 | Drugtech Corporation | Composition and method of use thereof |
US9023898B2 (en) | 2007-11-19 | 2015-05-05 | Fluoron Gmbh | Flushing solution |
US20100274215A1 (en) * | 2007-11-19 | 2010-10-28 | Fluoron Gmbh | Flushing solution |
US20100008996A1 (en) * | 2008-04-18 | 2010-01-14 | Novaliq Gmbh | Inhalative and instillative use of semifluorinated alkanes as an active substance carrier in the intrapulmonary area |
US8986738B2 (en) | 2008-04-18 | 2015-03-24 | Novaliq Gmbh | Inhalative and instillative use of semifluorinated alkanes as an active substance carrier in the intrapulmonary area |
US20110034414A1 (en) * | 2008-04-28 | 2011-02-10 | Al.Chi.Mi.A. S.R.L. | Fluoroalkyloxy alkanes, process for production and uses thereof |
EP2332525A1 (en) * | 2009-11-23 | 2011-06-15 | Novaliq GmbH | Pharmaceutical composition comprising propofol |
WO2011061332A1 (en) | 2009-11-23 | 2011-05-26 | Novaliq Gmbh | Pharmaceutical composition comprising propofol |
CN102753159A (zh) * | 2009-11-23 | 2012-10-24 | 诺瓦利克有限责任公司 | 包含异丙酚的药物组合物 |
US8796340B2 (en) | 2009-11-23 | 2014-08-05 | Novaliq Gmbh | Pharmaceutical composition comprising propofol |
AU2010320823B2 (en) * | 2009-11-23 | 2014-06-26 | Novaliq Gmbh | Pharmaceutical composition comprising propofol |
CN102753159B (zh) * | 2009-11-23 | 2014-03-12 | 诺瓦利克有限责任公司 | 包含异丙酚的药物组合物 |
US20110137285A1 (en) * | 2009-12-04 | 2011-06-09 | Al.Chi.Mi.A. S.R.L. | Kit of tamponing liquids and a method for the treatment of tears and/or detachments of the retina using such liquids |
EP2335692A1 (en) | 2009-12-04 | 2011-06-22 | AL.CHI.MI.A. S.r.l. | Silicone liquid and fluorinated liquid for sequential use in the treatment of retinal tears and/or detachments |
US8614178B2 (en) | 2009-12-14 | 2013-12-24 | Novaliq Gmbh | Pharmaceutical composition for treatment of dry eye syndrome |
CN102652022B (zh) * | 2009-12-14 | 2014-12-17 | 诺瓦利克有限责任公司 | 治疗干眼综合征的药物组合物 |
KR20120115977A (ko) * | 2009-12-14 | 2012-10-19 | 노바리크 게엠베하 | 안구건조증 치료용 약학 조성물 |
EP2335735A1 (en) * | 2009-12-14 | 2011-06-22 | Novaliq GmbH | Pharmaceutical composition for treatment of dry eye syndrome |
KR20160105533A (ko) * | 2009-12-14 | 2016-09-06 | 노바리크 게엠베하 | 안구건조증 치료용 약학 조성물 |
CN102652022A (zh) * | 2009-12-14 | 2012-08-29 | 诺瓦利克有限责任公司 | 治疗干眼综合征的药物组合物 |
WO2011073134A1 (en) | 2009-12-14 | 2011-06-23 | Novaliq Gmbh | Pharmaceutical composition for treatment of dry eye syndrome |
KR101722039B1 (ko) | 2009-12-14 | 2017-03-31 | 노바리크 게엠베하 | 안구건조증 치료용 약학 조성물 |
KR101652714B1 (ko) | 2009-12-14 | 2016-09-01 | 노바리크 게엠베하 | 안구건조증 치료용 약학 조성물 |
US10555953B2 (en) * | 2010-03-17 | 2020-02-11 | Novaliq Gmbh | Pharmaceutical composition for treatment of increased intraocular pressure |
US10525062B2 (en) | 2010-03-17 | 2020-01-07 | Novaliq Gmbh | Pharmaceutical composition for treatment of increased intraocular pressure |
US10045996B2 (en) | 2010-03-17 | 2018-08-14 | Novaliq Gmbh | Pharmaceutical composition for treatment of increased intraocular pressure |
US20190240234A1 (en) * | 2010-03-17 | 2019-08-08 | Novaliq Gmbh | Pharmaceutical composition for treatment of increased intraocular pressure |
US11324757B2 (en) | 2010-03-17 | 2022-05-10 | Novaliq Gmbh | Pharmaceutical composition for treatment of increased intraocular pressure |
WO2011151079A3 (de) * | 2010-06-02 | 2012-05-03 | Fluoron Gmbh | Zubereitung zur verwendung in der augenheilkunde und netzhautchirurgie |
US8865131B2 (en) | 2010-06-02 | 2014-10-21 | Fluoron Gmbh | Preparation for use in opthalmology and retinal surgery |
US11160865B2 (en) | 2010-10-20 | 2021-11-02 | Novaliq Gmbh | Liquid pharmaceutical composition for the delivery of active ingredients |
US9757459B2 (en) | 2010-10-20 | 2017-09-12 | Novaliq Gmbh | Liquid pharmaceutical composition for the delivery of active ingredients |
US9968678B2 (en) | 2010-10-20 | 2018-05-15 | Novaliq Gmbh | Liquid pharmaceutical composition for the delivery of active ingredients |
US9241900B2 (en) | 2010-11-11 | 2016-01-26 | Novaliq Gmbh | Liquid pharmaceutical composition for the treatment of a posterior eye disease |
EP3466408A1 (en) * | 2010-11-11 | 2019-04-10 | Novaliq GmbH | Liquid pharmaceutical composition for the treatment of a posterior eye disease |
AU2011328102B2 (en) * | 2010-11-11 | 2016-11-03 | Novaliq Gmbh | Liquid pharmaceutical composition for the treatment of a posterior eye disease |
US10064944B2 (en) | 2010-11-11 | 2018-09-04 | Novaliq Gmbh | Liquid pharmaceutical composition for the treatment of a posterior eye disease |
WO2012062834A1 (en) * | 2010-11-11 | 2012-05-18 | Novaliq Gmbh | Liquid pharmaceutical composition for the treatment of a posterior eye disease |
EP2462921A1 (en) * | 2010-11-11 | 2012-06-13 | Novaliq GmbH | Liquid pharmaceutical compositions for the treatment of a posterior eye disease |
AU2017200608B2 (en) * | 2010-11-11 | 2018-02-15 | Novaliq Gmbh | Liquid pharmaceutical composition for the treatment of a posterior eye disease |
US10130707B2 (en) | 2011-05-25 | 2018-11-20 | Novaliq Gmbh | Topical pharmaceutical composition based on semifluorinated alkanes |
AU2012260788B2 (en) * | 2011-05-25 | 2017-01-19 | Dermaliq Therapeutics, Inc. | Pharmaceutical composition for administration to nails |
US9308262B2 (en) | 2011-05-25 | 2016-04-12 | Novaliq Gmbh | Pharmaceutical composition for administration to nails |
CN107397718A (zh) * | 2011-05-25 | 2017-11-28 | 诺瓦利克有限责任公司 | 基于半氟化烷烃类的外用药物组合物 |
US10813999B2 (en) | 2011-05-25 | 2020-10-27 | Novaliq Gmbh | Topical pharmaceutical composition based on semifluorinated alkanes |
US11844836B2 (en) | 2011-05-25 | 2023-12-19 | Dermaliq Therapeutics, Inc. | Topical pharmaceutical composition based on semifluorinated alkanes |
US9757460B2 (en) | 2012-01-23 | 2017-09-12 | Novaliq Gmbh | Stabilised protein compositions based on semifluorinated alkanes |
USRE49758E1 (en) | 2012-01-23 | 2023-12-19 | Novaliq Gmbh | Stabilised protein compositions based on semifluorinated alkanes |
DE202013012753U1 (de) | 2012-09-12 | 2019-03-04 | Novaliq Gmbh | Zusammensetzungen semifluorierter Alkane zur Verwendung in der Behandlung von Keratoconjunctivitis Sicca |
US9770508B2 (en) | 2012-09-12 | 2017-09-26 | Novaliq Gmbh | Semifluorinated alkane compositions |
US10058615B2 (en) | 2012-09-12 | 2018-08-28 | Novaliq Gmbh | Semifluorinated alkane compositions |
EP4342537A2 (en) | 2012-09-12 | 2024-03-27 | Novaliq GmbH | Semifluorinated alkane compositions |
US11583513B2 (en) | 2012-09-12 | 2023-02-21 | Novaliq Gmbh | Semifluorinated alkane compositions |
US10576154B2 (en) | 2012-09-12 | 2020-03-03 | Novaliq Gmbh | Semifluorinated alkane compositions |
US12005033B2 (en) | 2012-09-12 | 2024-06-11 | Novaliq Gmbh | Compositions comprising mixtures of semifluorinated alkanes |
US10449164B2 (en) | 2012-09-12 | 2019-10-22 | Novaliq Gmbh | Methods of treating ocular disorders using semifluorinated alkanes |
EP3181119A1 (en) | 2012-09-12 | 2017-06-21 | Novaliq GmbH | Semifluorinated alkane compositions for use in the treatment of keratoconjunctivitis sicca |
EP2708228A1 (en) | 2012-09-12 | 2014-03-19 | Novaliq GmbH | Eye wash compositions |
EP3488847A1 (en) | 2012-09-12 | 2019-05-29 | Novaliq GmbH | Semifluorinated alkane compositions |
US10369117B2 (en) | 2012-09-12 | 2019-08-06 | Novaliq Gmbh | Compositions comprising mixtures of semifluorinated alkanes |
WO2014041071A1 (en) | 2012-09-12 | 2014-03-20 | Novaliq Gmbh | Semifluorinated alkane compositions |
US20160022648A1 (en) * | 2013-03-13 | 2016-01-28 | Santen Pharmaceutical Co., Ltd. | Therapeutic agent for meibomian gland dysfunction |
US11612590B2 (en) | 2013-03-13 | 2023-03-28 | Santen Pharmaceutical Co., Ltd. | Therapeutic agent for meibomian dysfunction |
US11951098B2 (en) | 2013-03-13 | 2024-04-09 | Santen Pharmaceutical Co., Ltd. | Therapeutic agent for meibomian dysfunction |
US20140315767A1 (en) * | 2013-04-22 | 2014-10-23 | Basf Se | Seal Compatibility Additive To Improve Fluoropolymer Seal Compatibility of Lubricant Compositions |
US20150191673A1 (en) * | 2013-04-22 | 2015-07-09 | Basf Se | Lubricating Oil Compositions Containing A Halide Seal Compatibility Additive And A Second Seal Compatibility Additive |
US10106759B2 (en) | 2013-04-22 | 2018-10-23 | Basf Se | Seal compatibility additive to improve fluoropolymer seal compatibility of lubricant compositions |
US10066186B2 (en) * | 2013-04-22 | 2018-09-04 | Basf Se | Lubricating oil compositions containing a halide seal compatibility additive and a second seal compatibility additive |
US11987623B2 (en) | 2013-07-23 | 2024-05-21 | Novaliq Gmbh | Stabilized antibody compositions |
US10273298B2 (en) | 2013-07-23 | 2019-04-30 | Novaliq Gmbh | Stabilized antibody compositions |
US20160264900A1 (en) * | 2013-11-05 | 2016-09-15 | Solvay Specialty Polymers Italy S.P.A. | Modified hydrocarbons |
EP2944324A1 (de) * | 2014-05-13 | 2015-11-18 | LTS LOHMANN Therapie-Systeme AG | Verwendung von semifluorierten Alkanen in transdermalen therapeutischen Systemen |
WO2015172872A1 (de) * | 2014-05-13 | 2015-11-19 | Lts Lohmann Therapie-Systeme Ag | Verwendung von semifluorierten alkanen in transdermalen therapeutischen systemen |
CN106456565A (zh) * | 2014-05-13 | 2017-02-22 | Lts勒曼治疗系统股份公司 | 半氟化烷烃在透皮治疗系统中的用途 |
WO2016082644A1 (en) * | 2014-11-26 | 2016-06-02 | The University Of Hong Kong | A semifluorinated alkane based cleaner for removing emulsified droplets in the eye to reduce the complications associated with the emulsification of silicone oil |
US11154513B2 (en) | 2015-09-30 | 2021-10-26 | Novaliq Gmbh | Semifluorinated compounds |
US11357738B2 (en) | 2015-09-30 | 2022-06-14 | Novaliq Gmbh | Semifluorinated compounds and their compositions |
US10682315B2 (en) | 2015-09-30 | 2020-06-16 | Novaliq Gmbh | Semifluorinated compounds and their compositions |
US10507132B2 (en) | 2016-06-23 | 2019-12-17 | Novaliq Gmbh | Topical administration method |
USRE50060E1 (en) | 2016-06-23 | 2024-07-30 | Novaliq Gmbh | Topical administration method |
US11684589B2 (en) | 2016-09-22 | 2023-06-27 | Novaliq Gmbh | Pharmaceutical compositions for use in the therapy of blepharitis |
US10813976B2 (en) | 2016-09-23 | 2020-10-27 | Novaliq Gmbh | Ophthalmic compositions comprising ciclosporin |
US11400132B2 (en) | 2016-09-23 | 2022-08-02 | Novaliq Gmbh | Ophthalmic compositions comprising ciclosporin |
CN106631681A (zh) * | 2016-11-29 | 2017-05-10 | 上海杰视医疗科技有限公司 | 含氟烷烃的纯化方法 |
CN106631681B (zh) * | 2016-11-29 | 2020-07-28 | 上海杰视医疗科技有限公司 | 含氟烷烃的纯化方法 |
US11273174B2 (en) | 2017-04-21 | 2022-03-15 | Novaliq Gmbh | Iodine compositions |
US10717691B2 (en) | 2017-05-05 | 2020-07-21 | Novaliq Gmbh | Process for the production of semifluorinated alkanes |
US11278503B2 (en) | 2017-05-12 | 2022-03-22 | Novaliq Gmbh | Pharmaceutical compositions comprising semifluorinated alkanes for the treatment of contact lense-related conditions |
US11723861B2 (en) | 2017-09-27 | 2023-08-15 | Novaliq Gmbh | Ophthalmic compositions comprising latanoprost for use in the treatment of ocular diseases |
US11896559B2 (en) | 2017-10-04 | 2024-02-13 | Novaliq Gmbh | Opthalmic compositions comprising F6H8 |
US11576893B2 (en) | 2018-03-02 | 2023-02-14 | Novaliq Gmbh | Pharmaceutical compositions comprising nebivolol |
WO2019185543A1 (en) * | 2018-03-28 | 2019-10-03 | Novaliq Gmbh | Pharmaceutical composition comprising timolol |
CN111867560A (zh) * | 2018-03-28 | 2020-10-30 | 诺瓦利克有限责任公司 | 包含噻吗洛尔的药物组合物 |
IL276888B1 (en) * | 2018-03-28 | 2024-08-01 | Novaliq Gmbh | Pharmaceutical compositions containing timolol |
JP7292567B2 (ja) | 2018-09-27 | 2023-06-19 | ダーマリック セラピューティクス, インコーポレーテッド | 局所日焼け止め製剤 |
US11510855B2 (en) | 2018-09-27 | 2022-11-29 | Dermaliq Therapeutics, Inc. | Topical sunscreen formulation |
US12029757B2 (en) | 2018-09-27 | 2024-07-09 | Dermaliq Therapeutics, Inc. | Lipid barrier repair |
JP2022501343A (ja) * | 2018-09-27 | 2022-01-06 | ノバリック ゲーエムベーハー | 局所日焼け止め製剤 |
US11413323B2 (en) | 2018-10-12 | 2022-08-16 | Novaliq Gmbh | Ophthalmic composition for treatment of dry eye disease |
US12059449B2 (en) | 2018-10-12 | 2024-08-13 | Novaliq Gmbh | Ophthalmic composition for treatment of dry eye disease |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6262126B1 (en) | Semi-fluorinated alkanes and their use | |
EP0150732B1 (en) | Phospholipid-emulsified prostaglandin compostion | |
EP0391637B1 (en) | Fluorinated microemulsion as oxygen carrier | |
EP0253472B1 (en) | Ophthalmic flurbiprofen preparation | |
CA2173321A1 (en) | Viscoelastic compositions of fluorinated organic compounds | |
EP0831775A1 (en) | Sustained release ophthalmic emulsions | |
EP3638643B1 (en) | Process for the preparation of semifluorinated alkanes using grignard reagents | |
RU2625301C2 (ru) | Офтальмологическая композиция | |
JPH03204853A (ja) | プロスタグランジン類縁体およびその脂肪乳剤 | |
US5171566A (en) | Flurbiprofen derivative ophthalmic preparation | |
EP0493677B1 (de) | Verwendung einer Perfluorocarbon(PFC)-Mixtur zur Herstellung einer Behandlungsflüssigkeit zum Wiederanlegen (Entfalten) abgelöster Netzhaut an die Aderhaut des Auges | |
CA2237048C (en) | Fluorinated alkanes and their uses | |
KR19990063430A (ko) | 고순도 스쿠알란, 그를 이용한 의약화장품원료 및 그의 제조방법 | |
AU725045B2 (en) | In vivo polymerizable ophthalmic compositions |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STCF | Information on status: patent grant |
Free format text: PATENTED CASE |
|
FPAY | Fee payment |
Year of fee payment: 4 |
|
FPAY | Fee payment |
Year of fee payment: 8 |
|
FPAY | Fee payment |
Year of fee payment: 12 |